It is known that hydrochloride of bevantolol represented by the following formula (1): ##STR1## shows cardio-selective .beta.-receptor blocking action (see U.S. Pat. No. 3,857,891, Japanese Patent Publication No. 52(1977)-33621, Japanese Patent Provisional Publication No. (1985) -246351) .
A process for the preparation of above bevantolol is disclosed in Japanese Patent Publication No. 52(1977)-33621, in which 3-(m-tolyloxy)-1,2-epoxypropane (TOEP) and .beta.-(3,4 -dimethoxyphenyl) ethylamine (HVA) are caused to react in equimolar amounts at 0 to 150.degree. C. for 10 minutes to 24 hours. This publication has no description as to yield of the desired compound. However, in Japanese Patent Provisional Publication No. 60(1985)-246351, it is described that a trace experiment of Example 2 of the above U.S. Patent results in a yield of not more than 50 % though the yield is variable (page 7, left upper column, lines 2 to 3 in the publication). The reason of such low yield is considered as follows:
When 3-(m-tolyloxy)-1,2-epoxypropane (hereinafter referred to as TOEP) represented by the following formula (2): ##STR2## reacts with .beta.-(3,4 -dimethoxyphenyl) ethylamine (hereinafter referred to as HVA) represented by the following formula (3): ##STR3## to give bevantolol of the above formula (1), the resultant bevantolol further reacts with TOEP of the starting material to produce a by-product represented by the following formula (4): ##STR4## Such consumption of the produced bevantolol causes its low yield.
Japanese Patent Provisional Publication No. 60(1985)-246351 discloses a process for preparing bevantolol comprising the steps of bringing the compound of the above formula (2) into contact with the compound of the above formula (3) in equimolar amounts, and adding a small amount of a seed of bevantolol to the reaction mixture. In the process, the obtained bevantolol is taken off from the reaction mixture by the addition of the seed for crystallization and the produced bevantolol is kept from reacting with TOEP of the starting material. By the procedure, it is intended that a yield of the bevantolol is increased. However, the process needs a long period of time in the adding procedure and the mixing procedure (Example 2 of the above-mentioned publication describes that it takes a period of time of not shorter than 100 hours from the mixing of starting materials to obtaining bevantolol). Further, the initial contact between TOEP and HVA is required to perform under cooling.